The goal of this research is to carry out a kinetic study of the alkylation of inorganic phosphate and a series of nucleosides, nucleotides, and polynucleotides by the diastereomeric bay region diol epoxides of the environmental carcinogen benzo(a)pyrene. Because guanine residues of RNA and DNA are more reactive toward alkylating agents than other bases, we plan to first determine the kinetic parameters for reaction of these diol epoxides with guanosine (G) and 5'-guanosine monophosphate (GMP). From plots of kobsd vs.(GMP), for instance, it will be possible to determine the reactive (or catalytic) ionization state of the nucleotide at a given pH. The rates of alkylation of poly G with the above diol epoxides as a function of pH will also be determined, and compared with the reactivities of G and GMP. Appropriate product analyses will also be carried out under the conditions that we use to determine the kinetic parameters. The reactivities of the individual nucleotide and nucleoside species along with that of the corresponding polynucleotide will help in determining the mechanisms by which epoxide alkylating agents react with the critical cellular reagents RNA and DNA. We are especially interested in determining the mechanism of alkylation at phosphate by nucleotides and polynucleotides, since such alkylation is believed to play an important role in the mutagenic and carcinogenic activities of epoxides and other alkylating agents. Ultimately, we plan to investigate the reactions of nucleic acid components with other carcinogenic and noncarcinogenic epoxides in order to determine if any correlation of reactivity vs. carcinogenicity exists.